The "bonanza" anticipated from the human genome sequencing project will include the elucidation of entirely new protein therapeutics, as well as the development of "traditional" drugs, by the processes of medical chemistry, acting on newly discovered targets. Exploitation of the full potential of this concept, termed "proteomics", will necessitate the rapid preparation in multi-milligram amounts of numerous proteins, and their analogs. Current recombinant methods are insufficient on many grounds, and are, additionally, restricted to natural sequences. This latter caveat can be overcome, in limited manner, via the preparation orf modified tRNA synthetases. Protein synthesis by chemical ligation of synthetic fragments has the potential to overcome these problems, yet the current methodology suffers from several drawbacks, which limit its general applicability. The principal problem with these procedures is that they are confined to the harsh conditions of the original Merrifield strategy; technical hurdles preclude application of milder, and more suitable, chemistry. In the phase I study, specific linkers and resins will be generated which overcome these deficiencies. In Phase II, the products from this program will be carefully evaluated for pharmaceut8ically relevance, and will then be introduced commercially. PROPOSED COMMERCIAL APPLICATIONS: There is enormous commercial potential, in pharmaceutical, basic and materials research, for the chemistry and products developed. Because of its limitations, chemical ligation is at present only practiced in a handful of laboratories. The wide spread application of the method is predicted to have a revolutionary effect; in the pharmaceutical industry alone it could serve as the basis for the combinatorial generation of enormous number of new drugs. The availability of a range of linkers, resins and methods compatible with Fmoc-chemistry will greatly enhance the viability of the method. Current projects anticipate sales of these consumables to rise rapidly with the popularity of the method, exceeding $2 million annually within 3 years. The sky is, almost literally, the limit for the valuation of the ultimate end products.